Background/Project Summary: Accurate assessments of the prevalence and population-based characteristics of fetal alcohol spectrum disorders (FASD) are sorely needed and long overdue for the U.S. mainstream population. The true extent, nature, and impact of FASD in the general population of the U.S., and in our schools, are currently unclear and/or unknown, although a recent estimate has placed the prevalence of FASD at 2 to 5%. Through screening, testing, and highly-structured interdisciplinary, lOM-recommended diagnostic procedures in 1st grade classes of three populations, we propose to: 1) assess the prevalence of FASD in two cohorts each within three specific 1st grade populations in the U.S. via two different applications of case control and random sampling methods; 2) define the exact characteristics of a) physical growth and morphology and b) neurodevelopmental characteristics U.S. children with and without FASD; 3) apply array comparative genomic hybridization (aCGH) techniques, in a nested study, to assess any major genetic factors (e.g. gene deletion syndromes) that may affect facial dysmorphia in cases of severe FASD (FAS or PFAS); 4) define specific maternal risk factors among mainstream American women for various levels of FASD; and 5) coordinate all data content, collection, formatting, and procedures with the Data Analysis Coordination Component (DACC) of the Collaboration of FASD Prevalence (CoFASP), and provide all data collected to the DACC of this NIAAA-funded initiative. Research will take place in: Great Falls, MT; Sioux Falls, SD; and ABC County, NC [pseudonym]. Three pilot studies have been carried out in Great Falls, and FASD has been estimated there at 1 to 2.5% of 1st grade children, a rate substantially higher than current estimates for the U.S. We are in a truly unique position at this time. As our epidemiologic methods and procedures have matured, the directions for innovation within future studies of U.S. populations are clear. Our experienced team of clinical researchers is cohesive, interdisciplinary, and expert, with 12 years experience in similar studies in the U.S. and foreign countries. This is an opportune time for this population-based study of the prevalence and characteristics of FASD in mainstream U.S. populations where FASD may be a substantially large, but underreported, public health problem. PUBLIC HEALTH RELEVANCE: The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) in the mainstream U.S. population are not known; recent estimates hold that FASD may affect 2 to 5% of all children. Innovative, active case ascertainment research on FASD in 1st grade children (and their mothers) of 3 representative U.S. populations will produce accurate measures of the magnitude, characteristics, and specific contextual etiology of FASD in mainstream populations. A better understanding of the public health and clinical impact of FASD in the general population will guide the way to better diagnosis, intervention, and prevention.